The synthesis of 4-(polyalkoxyphenyl)-pyrrolidin-2-ones is described in German Democratic Republic patent No. 119,229, as having a sedating, neuroleptic effect on the central nervous system.
4-(4-chlorophenyl)-pyrrolidin-2-one is mentioned in Japanese patent No. 7,016,692. It is not substituted at the nitrogen atom, and is said to have an anticonvulsive effect.
U.S. Pat. No. 4,443,616, describes the preparation of pyrrolidin-2-ones from 3-pyrrolidin-2-ones. The product is stated to have a CNS effect but this is not further explained in greater detail.
According to Japanese patent No. 3,246,328, aside from various CNS effects, N-acyllactams that are not substituted in the 4 position, also show antiamnestic effects in animal experiments. Our own experiments have shown that the cerebroprotective properties of these compounds are only weakly manifested especially when compared to the much more pronounced activity of the compounds of the present invention.
Moreover, N-dipropylacetyllactams with a 5-, 6- or 7-membered lactam ring are known e.g. from the German Democratic Republic patent No. 256 694. These lactams in animal experiment exhibit in addition to anticonvulsive effects, also antihypoxic and nootropic effects. On the other hand, the new compounds of the present invention show a decisive and, for the therapeutic application in man advantageous shift in the pharmacological spectrum, while having a decreased toxicity.
The compounds of the present invention show substantial advantages compared to known substances with nootropic activity, which were introduced some time ago in medical practice. For example, the antiamnestic effect of the compounds of the present invention is more than eight hundred times that of the standard nootropic drugs, piracetam and meclofexonate.